Saving Nigerian Mothers: Magnesium Sulphate for the treatment of Severe Preeclampsia and Eclampsia

J Tukur* B Ahonsi** A Karlyn** I Araoyinbo**

Presented at Asia Regional Meeting on Interventions for Impact in Essential Obstetric and Newborn Care Presenting by Sharif Mohammed Ismail Hossain 4-6 May, 2012 Dhaka, Bangladesh
*Aminu Kano Teaching Hospital,Kano, Nigeria; **Population Council, Nigeria

Introduction
Eclampsia is a common cause of maternal deaths worldwide especially in developing countries About 10% women have increased BP during pregnancy 2-8% pregnancies complicated by pre-eclampsia (PE) 10% pre-eclampsia carry on to eclampsia (E) 10-20% maternal deaths are associated with SPE/E (50,000) The Eclampsia Collaborative Trial and Magpie studies confirmed the efficacy of MgSO4 in the treatment of severe preeclampsia (SPE) and eclampsia. It showed
52-67% lower recurrence of seizures/fits than those treated with diazepam and phenytoin, respectively 58% prevents progression from SPE to E Reduce maternal deaths
WHO 2005, The lancet 1995, Khat et al 2006; Magpie trial 2002; ETCG 1995)

Background: Nigeria and Kano State

Category State Population MMR TFR CPR (modern) Age at marriage Adolescent begun childbearing National 37 140m 545/100,000 live births 5.7 10% 18.3 23% Kano State (north-west Nigeria) 9.4m (most populous) 1,000/100,000 live births 7.3 <5% <17 45%

IMR Hospitals provide maternity care

Use of Mgso4 in SPE/E

75/1,000 live births Not universal

110/1,000 live births 35

Occasionally in one specialist hospital

NPC 2008, 2009a; NDHS 2008

Background: Maternal deaths due to severe pre-eclampsia/eclampsia in Nigeria

In north-west Nigeria
31.3-46.4 maternal deaths contributed by eclampsia One study shows that 60% of the patients with eclampsia were<20 years and >78% of them were primigravida

In south and central Nigeria

34.4% maternal deaths contributed by eclampsia

In Nigeria, eclampsia is a common cause of maternal deaths Despite the evidences that Mgso4 prevents progression from SPE to eclampsia and reduce maternal deaths it was not universally used in Nigeria

Adam et al 2003, Kullim et al 2009, Tukur et al 2007 and 2008, SGO 2004

The study
Population Council launched the study in Kano State (most populous state) with support from MacArthur foundation Pre-post study in clinical setting without separate control group The study was approved by NIMR and Pop. Council IRB/ERRC

Interventions
Interventions were provided to 10 secondary level hospitals: Training of service providers Developing Mgso4 clinical protocol Supplying and introducing Mgso4
Training 25 staff trained (a doctor and a midwife from each facility) 2-day training
1st day: lectures on evidence-based management of hypertensive disorders of pregnancy, how to use Mgso4 and treatment of Mgso4 toxicity 2nd day: practical training at 25-bed eclamptic ward of MMSH, demonstration of use of Sphygmomanometer and urinalysis for proteinuria, injection of Mgso4 and toxicity monitoring

Intervention (cont)
The trained staff returned to their hospital and conducted stepdown training (trained 160 staff within 3 months) Developed Mgso4 clinical protocol Kano State eclampsia protocol.docx Participants were supplied with:
Mgso4 patella hammer (to assess deep tendon reflexes) and calcium gluconate (antidote of Mgso4 toxicity)

All 10 facilities (Kano, Bichi, Wudi, Gwarno, Rano, Minjibir, Tudun, Wada, Dogrewa, Rano and Rogo) commenced the use of the Mgso4 (Feb 2008- Jan 2009) Kano is urban and all other facilities are rural

Data collection and analysis

Baseline information collected retrospectively from 3 facilities for 1 year (Jan 1, 2007 -Dec 31, 2007) A form developed and used to collect information from each hospital (covers maternal socio-demographic characteristics, pattern of SPE/E and feto-maternal outcomes) 12 months data were collected monthly Two data review meetings were organized with hospital staff SPSS was used for data entry and analysis Multivariate analysis was performed to determine the factors associated with SPE/E and its case fatality rate (CFR) Relative standard error (RSE) was used as a measure of an estimated CFRs reliability and <30% was considered reliable

Baseline findings
Baseline findings from 3 general hospitals shows:
1233 mothers/patients took SPE/E services in the previous year 258 mothers died due to SPE/E Case fatality rate (CFR) was 20.9% Information on peri-natal mortality was not available Used diazepam to manage the SPE/E patients

Post-intervention findings: Socio-demographic characteristics of SPE/E patients

Basic characteristics Age <20 20-24 >24 Missing Parity Primigravida 1-5 >5 Missing Education No Primary Secondary+ Missing N Severe pre-eclampsia
(%)

Eclampsia

(%)

Total
(%)

38.8 38.8 20.4 2.0

52.1 31.3 14.9 1.7

51.5 31.7 15.1 1.7

61.2 26.5 12.2 0

73.5 14.3 10.2 2.0 49

60.3 35.2 3.3 1.1

74.1 17.8 6.3 1.8 996

60.4 34.8 3.7 1.1

74.1 17.6 6.5 1.8 1045

Behavior for ANC and time needed to reach the hospital after seizures/fits
Health seeking behavior for ANC Taken ANC Not taken ANC N Time needed to reach hospital 1 hours >1-3 hours >3 hours N Number of seizures/fits 0 1-2 3-4 (%) (%) (%) 73.1 66.2 55.4 20.2 6.7 104 21.9 11.9 370 28.4 16.2 303 Percentage 55.9 44.1 1045 Total (%) 60.2 23.7 16.1 942*

>4 (%) 47.3 12.2 31.5 165

* Information was missing for 103 cases

Outcomes of pregnancy, fetal & maternal deaths after administration of MgSO4

Outcomes Severe pre-eclampsia
(%)

Eclampsia (%)
76.7 16.2 2.3 4.8 2.3 94.4 3.3 12.8 83.6 3.6
996

Total (%)
75.6 16.8 2.3 5.3 2.3 94.1 3.6 12.3 83.5 4.1
1045

Pregnancy outcomes SVD CS AVD Missing Maternal outcomes Dead Alive Missing Foetal outcomes Dead Alive Missing
N

53.1 30.6 2.0 14.3 2.0 87.8 10.2 4.1 81.6 14.3
49

SVD-spontaneous vaginal delivery; CS-caesarian section; AVD-assisted vaginal delivery

Factors associated with eclampsia case fatality rate (CFR)

Variables CFR (95% CI) AOR (95% CI) Age 15-19 (ref) 1.5 (0.5, 2.6) 1.00 20 3.4 (1.8, 5.1) 1.46 (0.40, 5.42) Parity Primigravida (ref) 1.6 (0.6, 2.6) 1.00 1-5 2.9 (1.1, 4.6) 1.14 (0.31, 4.17) 6 8.6 (0.8, 18.0) 4.99 (0.77, 32.22)* Education None (ref) 2.4 (1.3, 3.5) 1.00 Primary 2.9 (0.1, 5.7) 1.18 (0.23, 6.23) Secondary /Higher 3.0 (1.1, 7.2) 1.00 (0.12, 8.25) Number of seizures/fits before presentation 2 (ref) 1.3 (0.3, 2.3) 1.00 3 2.9 (1.3, 4.4) 2.19 (0.63, 7.55) Recurrent seizures/fits after administration of loading dose No (ref) 1.8 (0.9, 2.6) 1.00 Yes 9.2 (2.1, 16.3) 7.65 (1.62, 36.03)*
* Significant at p<0.05; AOR: Adjusted odds ratio

Factors associated with eclampsia case fatality rate (CFR) cont

Variables CFR (95% CI) Mode of delivery CS (ref) 2.3 (0.1, 4.5) SVD 1.8 (0.9, 2.7) AVD 4.2 (4.0, 12.3) Condition Pre-eclampsia (ref) 2.3 (2.2, 6.7) Eclampsia 2.4 (1.4, 3.4) Time needed to reach hospital 1 hours (ref) 1.5(0.5, 2.5) >1 hour 3.1(1.4, 4.7) ANC taken or not Yes (ref) 1.8(0.7, 2.9) No 3.3(1.6, 5.1) AOR (95% CI) 1.00 0.77 (0.19, 3.09) 2.58 (0.16, 41.52)

1.00 0.59 (0.04, 8.94)

1.00 0.26(0.05, 1.33) 1.00 0.57(0.15, 2.13)

* Significant at p<0.05; AOR: Adjusted odds ratio

Factors associated with perinatal deaths

Factors Perinatal Mortality Adjusted OR % (95% CI) (95% CI) Recurrent seizures/fits after MgSO4 loading dose No (ref) 11.4 (9.5, 13.6) 1.00 Yes 27.7 (17.3, 40.2) 2.64 (1.25, 5.54)* Mode of delivery CS (ref) 8.5 (4.8, 13.7) 1.00 SVD 12.4 (10.2, 15.0) 1.24 (0.65, 2.36) AVD 29.2 (12.6, 51.1) 3.48 (1.12, 10.91)* Number of seizures/fits before presentation to hospital 0 (ref) 3.7 (1.0, 9.1) 1.00 1-2 10.4 (7.6, 14.1) 3.02 (0.90, 10.20) 3-4 13.4 (9.9, 17.9) 3.69 (1.09, 12.48) 5 17.9 (12.4, 24.5) 5.70 (1.63, 19.93)* Time before presentation to hospital 1hour (ref) 9.7 (7.5, 12.5) 1.00 1hour 16.3 (13.0, 20.2) 1.04 (0.65, 1.68)
*Significant at p<0.05; AOR: Adjusted Odds ratio; CS: Caesarean section; SVD: Spontaneous vaginal delivery; AVD: Assisted vaginal delivery

Comparison of case-fatality rates at baseline and during intervention period

Period All SPE/E cases (n) 1233 1045 Fatality due to SPE/E (n) 258 24 CFR (95% CI) (%) 20.9 (18.7, 23.2) 2.3 (1.5, 3.5) RSE (%) 5.5 20.2

Baseline Intervention

CFR= Case-Fatality Rate RSE= Relative standard error

Overall post-intervention findings

Post intervention findings from 10 hospitals shows:
1045 SPE/E patients treated in 12 months
996 eclamptic patients 49 severe pre-eclamptic patients

Mean time before presentation 8.4 hours Mean no. of seizures/fits 3.2 Case fatality rate (CFR) was 2.3% Perinatal deaths was 12.3% Reduction of CFR by 42.4% 2.2% patients showed toxic effect of Mgso4 but had no fatality Intervention findings further confirm that teenage, primigravidity and low educational attainment are risk factors for developing SPE/E

Utilization of results
By the 10th month of the project, the State Government took over the purchase of the drug and continued thereafter State Government replicated the intervention in other 25 facilities A follow on project is being continuing on injecting loading dose of Mgso4 by field workers (CHOs and CHEWs) and then referral to higher level and focusing on averting eclampsia by ante-natal detection of SPE and prompt treatment with MgSo4 and referral
The project demonstrated that:
Evidence based interventions could be introduced into new areas Engaging stakeholders can made a project sustainable Introduction of evidence based interventions usually replicable

Challenges
Stock-outs in a setting of free maternity scheme (all the facilities reported periods of stock-out of magnesium sulphate at least once during the 12 months of the project) Delays in reaching health facilities by the women

Thank you